Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 10, Issue 3, 2010

Sepsis remains a challenge for intensive care physicians and is one of the leading causes of death nowadays. This syndrome comprises a spectrum of conditions ranging from systemic inflammatory response syndrome (SIRS) to septic shock and multisystem organ failure (MSOF), the deadly forms of the disease. Although definite advances have been made in the knowledge regarding its pathogenesis and treatment and a de Read More

The continuous antigenic triggering has greatly contributed to the evolution of the immune system and, therefore, animals have developed cells able to cope with a broad variety of microbial antigens and or their toxins, e.g., endotoxins. At the same time, intestinal commensals have evolved along with human progress and introduction of new foods, thus empowering both regional and systemic immune response. In this revie Read More

Sepsis is one of the major health problems all over the word. Its pathophysiological mechanisms are not completely understood, but coagulation alterations are a hallmark of this syndrome. There is a clear exacerbation of coagulation and a suppression of control mechanisms of this process, including a reduction in fibrinolysis with consequent impairment of fibrin removal. The leading cause of these alterations is the proinflam Read More

Sepsis and multiple organ failure remain leading causes of death in intensive care patients. Recent advances in our understanding of the pathophysiology of these syndromes include a likely prominent role for mitochondria. Patient studies have shown that the degree of mitochondrial dysfunction is related to the eventual outcome. Associated mechanisms include damage to mitochondria or inhibition of the electron tra Read More

The sepsis syndrome represents an improper immune response to pathogens and is associated with an unacceptably high rate of mortality. Although supportive care is of benefit to the septic patient, there are no viable therapeutics available that target the immune system suitable for the whole septic population. Recently, using a physiologically relevant murine mouse model, the cannabiniod 2 receptor has been shown Read More

In the last few years, an important body of knowledge has been developed showing the pathophysiological relevance of the sublingual microcirculation in the development of multiorgan failure associated with sepsis. In addition to the compelling experimental evidence, the development of new videomicroscopic techniques allows now the evaluation of the microcirculation in critically ill patients. Consequently Read More

Septic shock is characterized by vasodilation and hypotension despite increased vasoconstrictors. While nitric oxide is known to be responsible for vasodilation, failure of vascular smooth muscle to constrict may be due in part to low plasma levels of vasopressin, a neurohypophyseal hormone. In the initial phase of septic shock, vasopressin concentration usually increases but then decreases to a significantly lower concentration Read More

Metabolic acidosis is very common in critically ill septic patients. Acidosis may be a result of the underlying pathophysiology, but it also may be the result of the way in which those patients are managed. Chloride-associated acidosis is frequent and is potentially aggravated during fluid resuscitation. The severity of metabolic acidosis is associated with poor clinical outcomes; however, it remains uncertain whether or not Read More

It is now clear that several members of the nuclear receptor superfamily are co-expressed by macrophages, lymphocytes and other cell types that are involved in the regulation of inflammatory and immune responses. Peroxisome proliferator-activated receptors (PPAR) and nuclear liver X receptors (LXR) are members of this family known to be activated by lipid derived endogenous ligands (such as fatty acids, eicosanoids Read More

Corticosteroids have been proposed for decades as adjunctive therapy of severe infections. These drugs have complex mechanisms of action involving anti-inflammatory and vasoactive properties. However, due to discordant results from clinical studies, the use of corticosteroids to treat patients with severe infections is still a matter of intense debate in the scientific and medical community. In the present article, we revie Read More

Sepsis remains one of the leading causes of death in intensive care units. Progressive cardiovascular failure is an important cause of the mortality. Septic patients with myocardial dysfunction have significantly higher mortality compared with patients without cardiovascular impairment. Myocardial dysfunction in sepsis is characterized by decreased contractility and impaired myocardial compliance. Experimental studies Read More

Sepsis is a complex clinical situation responsible for thousands of deaths annually in intensive care units around the globe. Despite all our progress in providing medical care to critically ill patients, mortality of severe forms of sepsis did not decrease as expected. Part of this phenomenon is due to our defective understanding about the host immune response to aggression by a microorganism, including the part played by the pat Read More

Acute critical illness is characterized by a hypermetabolic and catabolic response where profound endocrine, metabolic and immunologic changes are initiated and sustained through the activation, in part, of beta-adrenergic receptors. The modulation of beta-adrenergic receptor mediated endocrine, immunological and metabolic control may be beneficial in sepsis through a number of mechanisms. However, the complex in Read More